SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells

Xia, Suhong; Wu, Jingwen; Zhou, Wangdong; Zhang, Mingyu; Zhao, Kai; Liu, Jingmei; Tian, Dean; Liao, Jiazhi

doi:10.1038/s41419-021-03853-y

Cited by 30 publications

(14 citation statements)

References 49 publications

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“…html) 65 , EZH2 (1/800, 0.53 μg ml −1 ; https://www.cellsignal.com/products/ primary-antibodies/ezh2-d2c9-xp-rabbit-mab/5246) 66 , LOX1 (1/800, 1.25 μg ml −1 ; https://www.merckmillipore.com/FR/fr/product/Anti-LOX-1-clone-9E12.1,MM_NF-MABS186), CD68 (1/1,000, 0.7 μg ml −1 ; https://www.abcam. com/cd68-antibody-epr20545-ab213363.html) 67 , CD11b (1/200, 0.5 μg ml −1 ; https://www.cellsignal.com/products/primary-antibodies/cd11b-itgam-d6 x1n-rabbit-mab/49420) 68 , CD14 (1/50, 0.07 μg ml −1 ; https://www.cellmarque. com/antibodies/CM/2066/CD14_EPR3653) 69 , CD15 (1/100, 5 μg ml −1 ; https:// www.bdbiosciences.com/en-us/search-results?searchKey=555400) 70 and S100A9 (1/16,666, 0.06 μg ml −1 ; https://cdn.origene.com/datasheet/um800066.pdf).…”

Section: Methodsmentioning

confidence: 99%

Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma

Scholler

Perbost

Locke

et al. 2022

Nat Med

108

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Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory large B cell lymphoma (LBCL) and has treatment with similar efficacy across conventional LBCL subtypes. Toward patient stratification, we assessed whether tumor immune contexture influenced clinical outcomes after axi-cel. We evaluated the tumor microenvironment (TME) of 135 pre-treatment and post-treatment tumor biopsies taken from 51 patients in the ZUMA-1 phase 2 trial. We uncovered dynamic patterns that occurred within 2 weeks after axi-cel. The biological associations among Immunoscore (quantification of tumor-infiltrating T cell density), Immunosign 21 (expression of pre-defined immune gene panel) and cell subsets were validated in three independent LBCL datasets. In the ZUMA-1 trial samples, clinical response and overall survival were associated with pre-treatment immune contexture as characterized by Immunoscore and Immunosign 21. Circulating CAR T cell levels were associated with post-treatment TME T cell exhaustion. TME enriched for chemokines (CCL5 and CCL22), γ-chain receptor cytokines (IL-15, IL-7 and IL-21) and interferon-regulated molecules were associated with T cell infiltration and markers of activity. Finally, high density of regulatory T cells in pre-treatment TME associated with reduced axi-cel–related neurologic toxicity. These findings advance the understanding of LBCL TME characteristics associated with clinical responses to anti-CD19 CAR T cell therapy and could foster biomarker development and treatment optimization for patients with LBCL.

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Section: Methodsmentioning

confidence: 99%

Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma

Scholler

Perbost

Locke

et al. 2022

Nat Med

108

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“…qPCR results showed that when ALKBH5 was knocked down, the mRNA levels of SLC7A2 and CGB3 were downregulated both in MGC-803 and HGC-27 cell lines, indicating that they are regulated by ALKBH5. While there was no distinct relation between these two genes and of GC, SLC7A2 has been proven to be lowly expressed in hepatocellular carcinoma (HCC) and suppress the progress of HCC (50). Furthermore, CGB3 also acts as a tumor suppressor in cervical cancer (51).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5

Gao²,

Li³

et al. 2023

Front. Oncol.

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BackgroundN6-methyladenosine (m6A) RNA regulators play important roles in cancers, but their functions and mechanism have not been demonstrated clearly in gastric cancer (GC).MethodsIn this study, the GC samples with clinical information and RNA transcriptome were downloaded from The Cancer Genome Atlas database. The different expression genes were compared by the absolute value and median ± standard deviation. Samples with complete information were randomly divided into a training dataset and a test dataset. The differential expression genes (DEGs) between ALKBH5-low and ALKBH5-high subgroups were identified in the training dataset and constructed a risk model by Cox and least absolute shrinkage and selection operator regression. The model was testified in test datasets, overall survival (OS) was compared with the Kaplan–Meier method, and immune cell infiltration was calculated by the CIBERSORT algorithm in the low-risk and high-risk subgroups based on the model. The protein levels of ALKBH5 were detected with immunohistochemistry. The relative expression of messenger-ribonucleic acid (mRNA) was detected with quantitative polymerase chain reaction.ResultsALKBH5 was the only regulator whose expression was lower in tumor samples than that in normal samples. The low expression of ALKBH5 led to the poor OS of GC patients and seemed to be an independent protective factor. The model based on ALKBH5-regulated genes was validated in both datasets (training/test) and displayed a potential capacity to predict a clinical prognosis. Gene Ontology analysis implied that the DEGs were involved in the immune response; CIBERSORT results indicated that ALKBH5 and its related genes could alter the immune microenvironment of GC. The protein levels of ALKBH5 were verified as lowly expressed in GC tissues. SLC7A2 and CGB3 were downregulated with ALKBH5 knockdown.ConclusionsIn this study, we found that ALKBH5 might be a suppressor of GC; ALKBH5 and its related genes were latent biomarkers and immunotherapy targets.

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“…SLC7A2, a member of the solute carrier family, was related to the amino acid transmembrane transporter activity. A latest research by Xia et al [23] , demonstrated that overexpression of SLC7A2 suppressed the invasion and metastasis of hepatocellular carcinoma by regulating myeloid-derived suppressors cell recruitment. However, increased ELMO2 [24] and TPM4 [25] were related to the proliferation and metastasis of different cancers respectively, suggesting that they might contributed little to the regulation of miR-451 on RF/6A cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

miRNA-451 regulates rhesus choroid-retinal endothelial cell function and proteome profile

Wu¹,

Chen²,

Zhang³

et al. 2022

Int J Ophthalmol

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AIM: To evaluate the effect of miRNA-451 on rhesus macaque choroid-retinal endothelial (RF/6A) cell function and proteome profile. METHODS: The RF/6A cells were transfected with miRNA-451 mimic and inhibitor. The role of miRNA-451 on proliferation ability was evaluated by CCK-8 assay. Furthermore, iTRAQ quantitative proteomic analysis was applied to comprehensively illuminate the change of cellular proteins and biological function between different groups. RESULTS: In miRNA-451 overexpression group, cell proliferation of RF/6A decreased both at 24h and 48h; while in miRNA-451 inhibition group, on the contrary, RF/6A cell proliferation was increased at 48h. Based on iTRAQ quantitative proteomic analysis, 23 differentially expressed proteins (DEPs) were detected in the comparison of miRNA-451 mimic and mimic control-transfected RF/6A cells, and 30 DEPs were identified in the comparison of RF/6A cells transfected with miRNA-451 inhibitor and inhibitor control. DEPs such as GORASP2, KRT1, SLC7A2, RIC8A, DDX42, CAP1, PCBP2 might be closely related to the inhibitory effect of miRNA-451 on RF/6A cell proliferation, while PCYT1A, MGAT1, TUBB, MCU, SIL1, BID, MSH6 might account for the positive effect of miRNA-451 inhibitor on RF/6A cell growth. PTPN1, as the only protein exhibiting an opposite trend between miRNA-451 mimic and inhibitor-transfected cells, was most likely accountable for the inhibition of miRNA-451 mimic on RF/6A cell growth, and the promotion of miRNA-451 inhibitor on RF/6A cell proliferation. CONCLUSION: miRNA-451 overexpression can suppress the growth of RF/6A cells while knockdown of miRNA-451 can promote RF/6A cell viability. Among all DEPs, increased PTPN1 is most likely to account for the negative regulation of miRNA-451 on RF/6A proliferation. miRNA-451 can be a protective factor for neovascular disease of fundus via regulating choroid retinal endothelial cell function.

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SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells

Cited by 30 publications

References 49 publications

Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma

Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma

Identification and validation of signature for prognosis and immune microenvironment in gastric cancer based on m6A demethylase ALKBH5

miRNA-451 regulates rhesus choroid-retinal endothelial cell function and proteome profile

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